Mechanisms of Differentiation
Aspects relating to stem cells
Control of gene expression
Influence of the extracellular matrix and cell-cell interaction
Regeneration in different animals
Response to injury
Involves the capacity for renewal or recomposition
Tissues, organs or even organisms
Injury or damage
Resulting from pathologies, tumors, congenital diseases
or traumas (Sephel &Woodward, 2011).
5. Both the composition and the tissue properties are restored
Newly formed tissue is highly similar to the original tissue
Capable of proliferation and differentiation
By intense production of extracellular matrix, with large
amounts of collagen. (Hoffmann & Tsonis, 2013).
7. Mechanisms of Differentiation
Zygote, classified as totipotent, has the potential to originate any type of
cell, among more than two hundred cell types.
The cells gradually exhibit changes in the gene expression pattern.
In this stage the morphogens, soluble inductive factors, play a vital role in
Resulting in the development of a specific type of cell, i.e., cell
The differentiated cells keep the gene expression pattern stable, allowing
the expression of its characteristic phenotype (Robey; 2000).
8. Aspects relating to stem cells
Having capacity to differentiate into any types of cells.
In the adult organism the
Stem cells, called somatic, maintain the self-renewal capacity
9. Stem cells found in:
Fig 02: S tem cells in different organs (Tissue engineering and regenerative medicine,2010)
10. Deterministic and Stochastic Models
division of a stem cell
produces another stem
some stem cells generate
only stem cells
while others generate
Maintained in the adult organism by two main mechanisms (Levine &
11. In adult organisms the stem cells diminish over time, and older individuals
have a smaller amount of stem cells
With aging, mechanisms such as cell senescence and apoptosis are
apparently related to a decrease in the proliferative capacity of stem cells,
resulting from the accumulation of intrinsic (DNA mutations) and extrinsic
factors (changes in the microenvironment of stem cells)
factors (both internal and external), or mediators, are essential for the
maintenance of these cells
Can lead activation of the stem cells (Paunesku; 2001).
13. Inhibition of cyclin CDK
Cdks signal the cell that it is ready to pass into the next stage of the cell
There are some inhibitory proteins which blocks the cell cycle
In case of any damage or injury to cell
protein p53 is one of those responsible for blocking the cell cycle,
especially in the presence of DNA damage.
The increase in protein p53 induces the expression of p21 protein, which in
turn binds, through the amino-terminal region, to the cyclin-CDK (cyclin-
complex, usually responsible for cell cycle progression.
14. Control of gene expression
Certain genes are expressed throughout cell differentiation,
Gene expression takes place in transcription
Transcription factors are proteins that bind specifically to
DNA sequences, inducing or repressing gene expression,
The transcription factors act specifically at DNA sites, more specifically the
following sequences: promoters, or binding sites for the
RNA polymerase; enhancers and silencers,
Changes caused by methylation in general hinder gene expression (Torres &
15. Influence of the extracellular matrix and cell-cell
The ECM can be defined as an interconnected network of
macromolecules composed of
Adhesive proteins, structural fibrous proteins (collagen and elastin),
glycoproteins and specialized proteins (such as growth factors).
The influence of the extracellular matrix (ECM) in the
differentiation process involves the presence of factors immobilized
in the ECM
Involves undifferentiated cells returning to a less differentiated phase of its own
Dedifferentiation, cellular process in which undifferentiated cell reverts to
an earlier developmental stage, usually as part of a regenerative process.
This process allows the cell to proliferate again before redifferentiation, which
leads to the substitution of these cells that were lost.
18. Trans differentiation
Another natural mechanism that was observed for the first time in
the regeneration of the salamander lens over 100 years ago.
Trans differentiation, is a process where one mature somatic
cell transforms into another mature somatic cell.
Involves the conversion of a differentiated cell type into another cell
22. Regeneration in different animals
Some animals, such as starfish, planaria (flatworms) and Hydra have
significant regenerative capacity, and can originate complete specimens from
small fragments (Torres & Parfitt, 2007).
Fins and tail of zebrafish can regenerate.
This fish can also regenerate cardiac tissue after resection or the destruction of
cardiomyocyte's. (Santos, Wada, Carvalho; 2013).
27. Response to injury
The regenerative response is initiated through recognition of the loss
of tissue or local wound.
Which influence the activation of many processes for regeneration
28. Formation of the scar epithelium on wounds
It is an early response to the injury and consists of the migration of
epithelial cells to the tissue lesion (Schwank; 2002).
The wound epithelium plays an important role in subsequent
The formation of this wound epithelium is a target for a variety of
regulatory events (Levine & Tijan, 2003).
29. Tissue regeneration
Another type of regeneration that involves proliferation, close to the cut
It involves the restoration of tissues damaged
Classical examples of this type of regeneration in mammals are the skin,
bones and regeneration of the skeletal muscle (Torres & Parfitt, 2007).
The goal of regenerative medicine is to restore the cells, tissues and
structures that are lost or damaged after disease, injury or aging.
It is necessary to get a better idea of the cell differentiation, trans
differentiation, dedifferentiation and redifferentiation mechanisms that
occur in different contexts, such as during regeneration in animals.
The participation of stem cells and progenitor cells in this process is also
of considerable relevance.
The understanding of these mechanisms can facilitate highly relevant
therapeutic strategies in regenerative medicine and tissue engineering.
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